Can serum 8-hydroxy-2'-deoxyguanosine levels reflect the severity of pulmonary arterial hypertension?

Abstract

OBJECTIVE:Oxidative stress plays a pivotal role in the pathogenesis of pulmonary arterial hypertension. 8-Hydroxy-2'-deoxyguanosine is a sensitive biomarker that reflects the degree of oxidative damage to DNA. We investigated whether serum 8-Hydroxy-2'-deoxyguanosine is a clinically useful biomarker for the severity of pulmonary arterial hypertension. METHODS:We measured serum 8-Hydroxy-2'-deoxyguanosine levels in 25 patients (age 37±13 years, 68% women) diagnosed with idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension, or pulmonary arterial hypertension associated with congenital heart disease. The severity of pulmonary arterial hypertension was evaluated by six-min walking distance, World Health Organization functional class, and serum brain natriuretic peptide levels. Age and gender-matched 22 healthy subjects served as the control group. RESULTS:The comparison of 8-Hydroxy-2'-deoxyguanosine levels between patients and controls was not statistically different [(19.86±9.79) versus (18.80±3.94) ng/mL, p=0.622)]. However, there was a significant negative correlation between 8-Hydroxy-2'-deoxyguanosine levels and six-min walking distance (r= -0.614, p=0.001). Additionally, serum 8-Hydroxy-2'-deoxyguanosine levels in patients with functional class III-IV were significantly higher than those with functional class I-II (functional class III-IV 32.31±10.63 ng/mL versus functional class I-II 16.74±6.81 ng/mL, respectively, p=0.003). CONCLUSION:The 8-Hydroxy-2'-deoxyguanosine levels were significantly correlated with exercise capacity (six-min walking distance) and symptomatic status (functional class), both of which show the severity of pulmonary arterial hypertension in patients.

Circulating Reactive Oxygen Species in Adults with Congenital Heart Disease

“…The main finding of this study was that the blood levels of superoxide anion radical did not significantly differ between adults with CHD and their age- and gender-matched healthy controls. This finding is contrary to some other studies that claim the presence of oxidative stress in the peripheral blood of patients with CHD [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], but it is in accordance with three studies showing that there was no significant difference in oxidative stress in the peripheral blood of patients with CHD and healthy individuals [ 46 , 47 , 48 ].…”

“…In our study, only five adult patients with VSD were included; this subgroup was too small to perform a separate statistical analysis. In contrast, in most other studies on oxidative stress in the blood of patients with CHD, indirect nonspecific markers of oxidative stress [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ] were used, e.g., the assessment of the activity of oxidative and antioxidant enzymes (superoxide dismutase (SOD), catalase and glutathione peroxidase), levels of antioxidants (vitamin E, uric acid and selenium), levels of malondialdehyde (MDA) and protein carbonyl (PCO), plasma total oxidant status (TOS), total antioxidant capacity or status (TAC or TAS) and oxidative stress index (OSI) as well as the quantification of DNA damage assessed by alkaline comet assay in circulating lymphocytes and levels of 8-hydroxy-2′-deoxyguanosine.…”

“…However, endothelial function was examined with flow-mediated dilation (FMD) in the brachial artery, which is a conduit artery, and therefore it does not study the microcirculation. Using indirect assessments of oxidative stress, two groups [ 32 , 47 ] have already established a negative association between oxidative stress and exercise capacity in CHD. In our study, we were unable to confirm this finding as there was no statistically significant correlation between pVO 2 and superoxide anion radical levels directly measured by EPR in the blood of CHD patients.…”

Clinical significance of dynamics between oxidative stress levels during mechanical lung ventilation in premature infants with persistent pulmonary hypertension

“…By the 3rd-5th day of life, in children of group II, we noted an increase in the level of 8-OHdG -4.10±0.42 ng/ml while in group I the quantity of 8-OHdG index decreased -1.06±0.28 ng/ml, p<0.05 (Table 2). Thus, in the group of children with perinatal asphyxia, the level of the OS indicator increases, which also correlates with the average pressure in the pulmonary artery and the severity of PPH [10].…”

“…Perspective is studying the oxidative stress biomarkers in PPH and taking into account their dynamics when choosing a ventilation strategy in prematurely born infants. Our previous studies showed a moderate direct correlation between the biomarker of oxidative stressthe urinary 8-OHdG and mean pressure in the pulmonary artery on the 1 st and 3 rd -5 th days of life in prematurely born infants with asphyxia and with asphyxia in combination with RDS, which indicates the presence of a direct relationship between the severity of PPH and the severity of OS [10].…”